Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Endometrial Carcinoma to Immunotherapy and Chemotherapy

Abstract Background: Uterine Corpus Endometrial Carcinoma (UCEC) is the most common gynecological cancer. Here, we have investigated the significance of immune-related genes in predicting the prognosis and response of UCEC patients to immunotherapy and chemotherapy.Methods: Based on TCGA database, the single-sample gene-set enrichment analysis (ssGSEA scores) was utilized to obtain enrichment of 29 immune signatures. Univariate, multivariate Cox regression and LASSO regression analyses were performed to generate an immune-related prognostic signature (IRPS). The biological functions of IRPS-associated genes were evaluated using GSEA, TIMER Database analysis, Mutation analysis, IPS analysis, Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Immune Cell Abundance Identifier (ImmuCellAI). Potential small molecule drugs for UCEC were predicted using the connectivity map (Cmap). The mRNA and protein expression levels of IRPS-associated genes were tested via quantitative real-time PCR (qPCR) and immunohistology.Results: Two immune-related genes (CCL13 and KLRC1) were identified to construct the IRPS. Both genes were related to the prognosis of UCEC patients (P<0.05). The IRPS could distinguish patients with different prognosis and was closely associated with the infiltration of several types of immune cells. Our findings showed that patients with low IRPS benefited more from immunotherapy and developed stronger response to several chemotherapies, which was also confirmed by the results of ImmuCellAI. Finally, we identified three small molecular drugs that might improve the prognosis of patients with high IRPS. Conclusion: IRPS can be utilized to predict the prognosis of UCEC patients and provide valuable information about their therapeutic response to immunotherapy and chemotherapy.